This Center grant requests funding for seven Core facilities to support a broadly-based research program in the study of mental retardation and developmental disabilities. The seven Core facilities are: Administrative, Proteomics, Cellular Neuroscience, Imaging, Gene Manipulation, Molecular Genetics, and Cell Sorter. The cores have undergone major development and support 123 research projects and 73 investigators. The research is in two programmatic areas (Neuroscience and Genetics). In Neuroscience, there are two major programs (Basic Neuroscience and Clinical/Translational Neuroscience). The Basic Neuroscience Program, directed by the Center Director, Dr. Michael Greenberg, consists of 47 investigators whose research efforts span a broad spectrum of interdigitated research in molecular neuroscience and systems neurobiology. A research project in Basic Neuroscience, proposed in this grant as a "New Program," addresses " the function of the GTPase regulatory enzyme, ephexin5, in synapse formation and dendritic spine development" (Mustafa Sahin, M.D., Ph.D.). A second major program in Neuroscience, i.e., Clinical/Translational Neuroscience, directed by Dr. Scott Pomeroy, includes 15 investigators whose research efforts include such areas as neuro-oncology, brain injury, brain behavior and brain development in neonates, human visual development, HIV, heart disease, surgery, and the developing brain, in vivo studies of brain development, neurocognitive development, developmental neuropsychology and learning disabilities, and endogenous and exogenous pxins and brain development. These areas of clinical research interdigitate with the basic research in the MRDDRC. In Genetics, directed by Dr. Louis Kunkel, 11 investigators are studying the molecular genetics of neuromuscular disease and human cerebral cortical development, the molecular basis of genetic disorders, retinal development and degenerative disorders, signal transduction, muscle stem cells, the genetics of complex traits and inherited musculoskeletal disorders. The multidisciplinary approaches to the research of this MRDDRC include the various basic science disciplines within Genetics and Neuroscience, and the clinical science fields of Neurology, Pediatrics, Neonatology, Infectious Disease, Endocrinology, Metabolism, Genetics, Cardiology, Neuropathology, Ophthalmology, Psychiatry, and Psychology. The research programs are housed in over 142,000 sq. ft. in two research buildings at Children's Hospital and several other facilities within the Harvard-Longwood Medical Area.